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Reverse engineering molecular hypergraphs

Published: 07 October 2012 Publication History

Abstract

Analysis of molecular interaction networks is pervasive in systems biology. This research relies almost entirely on graphs for modeling interactions. However, edges in graphs cannot represent multi-way interactions among molecules, which occur very often within cells. Hypergraphs may be better representations for such interactions, since hyperedges can naturally represent relationships among multiple molecules.
Here we propose using hypergraphs to capture the uncertainty that is inherent in reverse engineering gene-gene networks from systems biology datasets. Some subsets of nodes may induce highly varying subgraphs across an ensemble of high-scoring networks inferred by a reverse engineering algorithm. We provide a novel formulation of hyperedges to capture this uncertainty in network topology. We propose a clustering-based approach to discover hyperedges.
We show that our approach can recover hyperedges planted in synthetic datasets with high precision and recall. We apply our techniques to a published dataset of pathway structures inferred from quantitative genetic interaction data in S. cerevisiae related to the unfolded protein response in the endoplasmic reticulum (ER). Our approach discovers several hyperedges that capture the uncertain connectivity of genes in specific pathways and complexes related to the ER.
Our work demonstrates that molecular interaction hypergraphs are powerful representations for capturing uncertainty in network structure. The hyperedges we discover directly suggest groups of genes for which further experiments may be required in order to precisely discover interaction patterns.

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  • (2013)MFMSProceedings of the 12th International Workshop on Data Mining in Bioinformatics10.1145/2500863.2500869(51-57)Online publication date: 11-Aug-2013

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cover image ACM Conferences
BCB '12: Proceedings of the ACM Conference on Bioinformatics, Computational Biology and Biomedicine
October 2012
725 pages
ISBN:9781450316705
DOI:10.1145/2382936
Permission to make digital or hard copies of all or part of this work for personal or classroom use is granted without fee provided that copies are not made or distributed for profit or commercial advantage and that copies bear this notice and the full citation on the first page. Copyrights for components of this work owned by others than ACM must be honored. Abstracting with credit is permitted. To copy otherwise, or republish, to post on servers or to redistribute to lists, requires prior specific permission and/or a fee. Request permissions from [email protected]

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Published: 07 October 2012

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BCB '12 Paper Acceptance Rate 33 of 159 submissions, 21%;
Overall Acceptance Rate 254 of 885 submissions, 29%

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  • (2013)MFMSProceedings of the 12th International Workshop on Data Mining in Bioinformatics10.1145/2500863.2500869(51-57)Online publication date: 11-Aug-2013

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